Vanderbilt University School of
Osteen, Kevin G. , Ph.D.
Professor of Obstetrics and Gynecology
Professor of Pathology, Microbiology and Immunology
Pierre Soupart Chair in Obstetrics and Gynecology
Adjunct Professor of Obstetrics and Gynecology at Meharry Medical College
Phone Number: 615-322-4196
S-1212 Medical Center North
B-1100 MCN 2519
reproductive medicine, human endometium, endometrial dysfunction, endometriosis, progesterone action, environmental endocrine disruptors, developmental exposure
Among normal adult tissues, the endometrial lining of the human uterus undergoes perhaps the most dynamic cycle of steroid controlled growth, differentiation and tissue breakdown. The rate of estrogen-driven cell growth during the proliferative phase of the menstrual cycle rivals that of many tumors while progesterone inhibits endometrial growth and appears to provide protection from the development of both benign diseases and certain neoplasms. Ovarian steroids clearly control the endometrium and endometrial activity; however, steroids alone cannot account for the entire orchestration of such well-controlled and often focal patterns of cellular proliferation and differentiation which are observed. To better understand steroid sensitive tissue behavior, my research laboratory has focused on the endometrium as a model to identify interrelationships between steroid action and stromal-epithelial cell communication via specific paracrine factors. Of special interest to us are the cellular and molecular mechanisms which control steroid-dependent versus steroid-independent expressions of metalloproteinases. These enzymes are necessary for degradation of extracellular matrix proteins and play important roles in the extensive tissue remodeling which normally occurs during the menstrual cycle as well as during establishment of the hemochorial placenta. Metalloproteinases may also contribute to the pathophysiology of endometrial dysfunction including abnormal bleeding, defects of placentation and the extrauterine disease endometriosis. Recently, we have extended our studies to investigate altered metalloproteinase gene and protein expression relative to the reproductive toxicology of dioxin.
Bruner-Tran, KL, Herington, JL, Duleba, AJ, Taylor, HS, Osteen, KG. Medical management of endometriosis: emerging evidence linking inflammation to disease pathophysiology. Minerva Ginecol, 65(2), 199-213, 2013.
Halder, SK, Osteen, KG, Al-Hendy, A. 1,25-dihydroxyvitamin d3 reduces extracellular matrix-associated protein expression in human uterine fibroid cells. Biol Reprod, 89(6), 150, 2013.
Halder, SK, Osteen, KG, Al-Hendy, A. Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells. Hum Reprod, 28(9), 2407-16, 2013.
Herington, JL, Glore, DR, Lucas, JA, Osteen, KG, Bruner-Tran, KL. Dietary fish oil supplementation inhibits formation of endometriosis-associated adhesions in a chimeric mouse model. Fertil Steril, 99(2), 543-50, 2013.
Sokalska, A, Anderson, M, Villanueva, J, Ortega, I, Bruner-Tran, KL, Osteen, KG, Duleba, AJ. Effects of simvastatin on retinoic acid system in primary human endometrial stromal cells and in a chimeric model of human endometriosis. J Clin Endocrinol Metab, 98(3), E463-71, 2013.
Villanueva, JA, Sokalska, A, Cress, AB, Ortega, I, Bruner-Tran, KL, Osteen, KG, Duleba, AJ. Resveratrol potentiates effect of simvastatin on inhibition of mevalonate pathway in human endometrial stromal cells. J Clin Endocrinol Metab, 98(3), E455-62, 2013.
Bruner-Tran, KL, Resuehr, D, Ding, T, Lucas, JA, Osteen, KG. The Role of Endocrine Disruptors in the Epigenetics of Reproductive Disease and Dysfunction: Potential Relevance to Humans. Curr Obstet Gynecol Rep, 1(3), 116-123, 2012.
Cakmak, H, Basar, M, Seval-Celik, Y, Osteen, KG, Duleba, AJ, Taylor, HS, Lockwood, CJ, Arici, A. Statins inhibit monocyte chemotactic protein 1 expression in endometriosis. Reprod Sci, 19(6), 572-9, 2012.
Resuehr, D, Glore, DR, Taylor, HS, Bruner-Tran, KL, Osteen, KG. Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Fertil Steril, 98(4), 948-56.e1, 2012.
Sokalska, A, Cress, A, Bruner-Tran, KL, Osteen, KG, Taylor, HS, Ortega, I, Duleba, AJ. Simvastatin decreases invasiveness of human endometrial stromal cells. Biol Reprod, 87(1), 2, 1-6, 2012.
Herington, JL, Bruner-Tran, KL, Lucas, JA, Osteen, KG. Immune interactions in endometriosis. Expert Rev Clin Immunol, 7(5), 611-26, 2011.
McConaha, ME, Ding, T, Lucas, JA, Arosh, JA, Osteen, KG, Bruner-Tran, KL. Preconception omega-3 fatty acid supplementation of adult male mice with a history of developmental TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) exposure prevents preterm birth in unexposed female partners. Reproduction, , , 2011.
Taylor, HS, Osteen, KG, Bruner-Tran, KL, Krikun, G, Sokalska, A, Duleba, AJ. Novel Therapies Targeting Endometriosis. Reprod Sci, , , 2011.
Bruner-Tran, K, Osteen, KG, Taylor, HS, Sokalska, A, Haines, K, Duleba, AJ. Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro. Biol Reprod, , , 2010.
Bruner-Tran, KL, Carvalho-Macedo, AC, Duleba, AJ, Crispens, MA, Osteen, KG. Experimental endometriosis in immunocompromised mice after adoptive transfer of human leukocytes. Fertil Steril, 93(8), 2519-24, 2010. PMCID:2875884
Bruner-Tran, KL, Ding, T, Osteen, KG. Dioxin and endometrial progesterone resistance. Semin Reprod Med, 28(1), 59-68, 2010. PMCID:2875884
Bruner-Tran, KL, Osteen, KG. Dioxin-like PCBs and endometriosis. Syst Biol Reprod Med, 56(2), 132-46, 2010. PMCID:2867352
Bruner-Tran, KL, Osteen, KG. Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations. Reprod Toxicol, , , 2010.
Ding, T, McConaha, M, Boyd, KL, Osteen, KG, Bruner-Tran, KL. Developmental dioxin exposure of either parent is associated with an increased risk of preterm birth in adult mice. Reprod Toxicol, , , 2010.
Herington, JL, Crispens, MA, Carvalho-Macedo, AC, Camargos, AF, Lebovic, DI, Bruner-Tran, KL, Osteen, KG. Development and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis. Fertil Steril, , , 2010.
Krikun, G, Hu, Z, Osteen, K, Bruner-Tran, KL, Schatz, F, Taylor, HS, Toti, P, Arcuri, F, Konigsberg, W, Garen, A, Booth, CJ, Lockwood, CJ. The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor causing regression of endometriosis. Am J Pathol, 176(2), 1050-6, 2010. PMCID:2875884
Bruner-Tran, KL, Osteen, KG, Duleba, AJ. Simvastatin protects against the development of endometriosis in a nude mouse model. J Clin Endocrinol Metab, 94(7), 2489-94, 2009. PMCID:2708947
Bruner-Tran, KL, Yeaman, GR, Crispens, MA, Igarashi, TM, Osteen, KG. Dioxin may promote inflammation-related development of endometriosis. Fertil Steril, 89(5 Suppl), 1287-98, 2008. PMCID:2430157
Bruner-Tran, KL, Zhang, Z, Eisenberg, E, Winneker, RC, Osteen, KG. Down-regulation of Endometrial MMP-3 and MMP-7 Expression in vitro and Therapeutic
Regression of Experimental Endometriosis in vivo by a Novel Nonsteroidal Progesterone Receptor Agonist,
Tanaproget. J Clin Endocrinol Metab, 91(4), 1554-60, 2006.
Nayyar, T, Bruner-Tran, KL, Piestrzeniewicz-Ulanska, D, Osteen, KG. Developmental exposure of mice to TCDD elicits a similar uterine phenotype
in adult animals as observed in women with endometriosis. Reprod Toxicol, 23(3), 326-36, 2006. PMCID:1885235
Harris, HA, Bruner-Tran, KL, Zhang, X, Osteen, KG, Lyttle, CR. A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis. Hum Reprod, 20(4), 936-41, 2005. PMCID:1885235
Igarashi, TM, Bruner-Tran, KL, Yeaman, GR, Lessey, BA, Edwards, DP, Eisenberg, E, Osteen, KG. Reduced expression of progesterone receptor-B in the endometrium of women with
endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fertil Steril, 84(1), 67-74, 2005.
Kurita, T, Medina, R, Schabel, AB, Young, P, Gama, P, Parekh, TV, Brody, J, Cunha, GR, Osteen, KG, Bruner-Tran, KL, Gold, LI. The activation function-1 domain of estrogen receptor alpha in uterine stromal cells is required for mouse but not human uterine epithelial response to estrogen. Differentiation, 73(6), 313-22, 2005. PMCID:1885235
Osteen, KG, Bruner-Tran, KL, Eisenberg, E. Reduced progesterone action during endometrial maturation: a potential risk
factor for the development of endometriosis. Fertil Steril, 83(3), 529-37, 2005.
Osteen, KG, Bruner-Tran, KL, Eisenberg, E. Endometrial biology and the etiology of endometriosis. Fertil Steril, 84(1), 33-4; discussion 38-9, 2005.
Osteen, KG, Igarashi, TM, Yeaman, GR, Bruner-Tran, KL. Steroid and cytokine regulation of matrix metalloproteinases and the pathophysiology
of endometriosis. Gynecol Obstet Invest, 57(1), 53-4, 2004.
Apparao, KB, Illera MJ, Beyler SA, Olson GE, Osteen KG, Corjay MH, Boggess K, Lessey, BA. Regulated expression of osteopontin in the peri-implantation rabbit uterus. Biol Reprod, 68, 1484-1490, 2003.
Curry, TE, Osteen, KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev, 24(4), 428-65, 2003. PMCID:1885235
Fortin M, Lepine M, Page M, Osteen K, Massie B, Hugo P, Steff A-M. An improved mouse model for endometriosis allows noninvasive assessment of lesion implantation and development. Fertil and Steril, 80,Suppl 2, 832-838, 2003.
Fortin, M, L??pine, M, Pag??, M, Osteen, K, Massie, B, Hugo, P, Steff, AM. An improved mouse model for endometriosis allows noninvasive assessment of lesion implantation and development. Fertil Steril, 80 Suppl 2, 832-8, 2003. PMCID:1885235
Hull ML, Charnock-Jones DS, Chan CL, Bruner-Tran KL, Osteen KG, Tom BD, Fan TP, Smith SK. Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab, 88, 2889-2899, 2003.
Hull, ML, Charnock-Jones, DS, Chan, CL, Bruner-Tran, KL, Osteen, KG, Tom, BD, Fan, TP, Smith, SK. Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab, 88(6), 2889-99, 2003. PMCID:1885235
Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice, LC. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology, 144, 2870-2881, 2003.
Osteen, Kevin G, Igarashi, Toshio M, Bruner-Tran, Kaylon L. Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression. Front Biosci, 8, d78-86, 2003.
Osteen, Kevin G, Yeaman, Grant R, Bruner-Tran, Kaylon L. Matrix metalloproteinases and endometriosis. Semin Reprod Med, 21(2), 155-64, 2003.
Bruner-Tran, KL, Webster-Clair, D, Osteen, KG. Experimental endometriosis: the nude mouse as a xenographic host. Ann N Y Acad Sci, 955, 328-39; discussion 340-2, 396-406, 2002.
Bruner-Tran, Kaylon L, Eisenberg, Esther, Yeaman, Grant R, Anderson, Ted A, McBean, Judith, Osteen, Kevin G. Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice. J Clin Endocrinol Metab, 87(10), 4782-91, 2002.
Cornet PB, Picquet C, Lemoine P, Osteen KG, Bruner-Tran KL, Tabibzadeh S, Courtoy PJ, Eeckhout Y, Marbaix E, Henriet P. Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloprotineases. Biol Chem , 277, 42496-42504, 2002.
Osteen, KG, Bruner-Tran, KL, Keller, NR, Eisenberg, E. Progesterone-mediated endometrial maturation limits matrix metalloproteinase
(MMP) expression in an inflammatory-like environment: a regulatory system altered in endometriosis. Ann N Y Acad Sci, 955, 37-47; discussion 86-8, 396-406, 2002.
Osteen, KG, Bruner-Tran, KL, Ong, D, Eisenberg, E. Paracrine mediators of endometrial matrix metalloproteinase expression: potential
targets for progestin-based treatment of endometriosis. Ann N Y Acad Sci, 955, 139-46; discussion 157-8, 396-406, 2002.
Bofinger DP, Feng L, Chi LH, Love J, Stephen FD, Sutter TR, Osteen KG, Costich TG, Batt RE, Koury ST, Olson JR. Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of human endometrium. Toxicol Sci, 62, 299-314, 2001.
Curry TE Jr, Osteen KG. Cyclic changes in the matrix metalloproteinase system in the ovary and uterus. Biol Reprod, 64, 1285-1296, 2001.
Keller, N R, Sierra-Rivera, E, Eisenberg, E, Osteen, K G. Progesterone exposure prevents matrix metalloproteinase-3 (MMP-3) stimulation by interleukin-1alpha in human endometrial stromal cells. J Clin Endocrinol Metab, 85(4), 1611-9, 2000.
Zheng, W L, Sierra-Rivera, E, Luan, J, Osteen, K G, Ong, D E. Retinoic acid synthesis and expression of cellular retinol-binding protein and cellular retinoic acid-binding protein type II are concurrent with decidualization of rat uterine stromal cells. Endocrinology, 141(2), 802-8, 2000.
Bruner, K L, Eisenberg, E, Gorstein, F, Osteen, K G. Progesterone and transforming growth factor-beta coordinately regulate suppression of endometrial matrix metalloproteinases in a model of experimental endometriosis. Steroids, 64(9), 648-53, 1999.
Bruner-Tran, K L, Rier, S E, Eisenberg, E, Osteen, K G. The potential role of environmental toxins in the pathophysiology of endometriosis. Gynecol Obstet Invest, 48 Suppl 1, 45-56, 1999.
Osteen, K G, Keller, N R, Feltus, F A, Melner, M H. Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium. Gynecol Obstet Invest, 48 Suppl 1, 2-13, 1999.
Zheng, W L, Bucco, R A, Sierra-Rievera, E, Osteen, K G, Melner, M H, Ong, D E. Synthesis of retinoic acid by rat ovarian cells that express cellular retinoic acid-binding protein-II. Biol Reprod, 60(1), 110-4, 1999.
Bruner, K L, Matrisian, L M, Rodgers, W H, Gorstein, F, Osteen, K G. Suppression of matrix metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice. J Clin Invest, 99(12), 2851-7, 1997. PMCID:508135
Bucco, R A, Zheng, W L, Davis, J T, Sierra-Rivera, E, Osteen, K G, Chaudhary, A K, Ong, D E. Cellular retinoic acid-binding protein(II) presence in rat uterine epithelial cells correlates with their synthesis of retinoic acid. Biochemistry, 36(13), 4009-14, 1997.
Osteen, K G, Sierra-Rivera, E. Does disruption of immune and endocrine systems by environmental toxins contribute to development of endometriosis. Semin Reprod Endocrinol, 15(3), 301-8, 1997.
Osteen, K G, Sierra-Rivera, E, Keller, N R, Fox, D B. Interleukin-1 alpha opposes progesterone-mediated suppression of MMP-7. A possible role of this cytokine during human implantation. Ann N Y Acad Sci, 828, 137-45, 1997.
Bucco, R A, Zheng, W L, Wardlaw, S A, Davis, J T, Sierra-Rivera, E, Osteen, K G, Melner, M H, Kakkad, B P, Ong, D E. Regulation and localization of cellular retinol-binding protein, retinol-binding protein, cellular retinoic acid-binding protein (CRABP), and CRABP II in the uterus of the pseudopregnant rat. Endocrinology, 137(7), 3111-22, 1996.
Osteen, K G, Bruner, K L, Sharpe-Timms, K L. Steroid and growth factor regulation of matrix metalloproteinase expression and endometriosis. Semin Reprod Endocrinol, 14(3), 247-55, 1996.
Bruner, K L, Rodgers, W H, Gold, L I, Korc, M, Hargrove, J T, Matrisian, L M, Osteen, K G. Transforming growth factor beta mediates the progesterone suppression of an epithelial metalloproteinase by adjacent stroma in the human endometrium. Proc Natl Acad Sci U S A, 92(16), 7362-6, 1995. PMCID:41339
Matrisian, L M, Gaire, M, Rodgers, W H, Osteen, K G. Metalloproteinase expression and hormonal regulation during tissue remodeling in the cycling human endometrium. Contrib Nephrol, 107, 94-100, 1994.
Osteen, K G, Rodgers, W H, Gaire, M, Hargrove, J T, Gorstein, F, Matrisian, L M. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc Natl Acad Sci U S A, 91(21), 10129-33, 1994. PMCID:44971
Rodgers, WH, Matrisian, LM, Giudice, LC, Dsupin, B,
Svitek, C, Gorstein, F, and KG Osteen. Patterns of
metalloproteinase expression in cycling endometrium imply
functions and regulation by steroids. J. Clin. Invest., 94, 946-953, 1994.
Bastias, MC, Kamijo, H, Osteen, KG. Assessment of human sperm functional changes after in-vitro coincubation with
cells retrieved from the human female reproductive tract. Hum Reprod, 8(10), 1670-7, 1993.
Freeman, MR, Bastias, MC, Hill, GA, Osteen, KG. Coculture of mouse embryos with cells isolated from the human ovarian follicle,
oviduct, and uterine endometrium. Fertil Steril, 59(1), 138-42, 1993.
Rodgers, W H, Osteen, K G, Matrisian, L M, Navre, M, Giudice, L C, Gorstein, F. Expression and localization of matrilysin, a matrix metalloproteinase, in human endometrium during the reproductive cycle. Am J Obstet Gynecol, 168(1 Pt 1), 253-60, 1993.
Vasquez, JM, Eisenberg, E, Osteen, KG, Hickerson, D, Diamond, MP. Laparoscopic ablation of endometriosis using the cavitational ultrasonic surgical
aspirator. J Am Assoc Gynecol Laparosc, 1(1), 36-42, 1993.
Hill, GA, Osteen, KG. The effect of insulin on in vitro progesterone production of human granulosa
cells. Int J Fertil, 37(2), 93-8, 1992.
Osteen, KG, Anderson, TL, Schwartz, K, Hargrove, JT, Gorstein, F. Distribution of tumor-associated glycoprotein-72 (TAG-72) expression throughout
the normal female reproductive tract. Int J Gynecol Pathol, 11(3), 216-20, 1992.
Osteen, KG, Anderson, TL. Effect of estrogen on human endometrial epithelial cell growth and differentiation
in vitro. Steroids, 56(5), 279-83, 1991.
Anderson, TL, Gorstein, F, Osteen, KG. Stromal-epithelial cell communication, growth factors, and tissue regulation. Lab Invest, 62(5), 519-21, 1990.
Herbert, CM, Hill, GA, Maxson, WS, Wentz, AC, Osteen, KG. Use of a sensitive urine pregnancy test before endometrial biopsies taken in
the late luteal phase. Fertil Steril, 53(1), 162-4, 1990.
Osteen, KG, Anderson, TL, Hargrove, JT, Hill, GA, Gorstein, F. Epithelial cells from normal human endometrium express a tumor-associated glycoprotein
(TAG-72) epitope in vitro. Am J Obstet Gynecol, 163(2), 479-84, 1990.
Segars, JH, Hill, GA, Bryan, SH, Herbert, CM, Osteen, KG, Rogers, BJ, Wentz, AC. The use of gonadotropin releasing hormone agonist (GnRHa) in good responders
undergoing repeat in vitro fertilization/embryo transfer (IVF/ET). J In Vitro Fert Embryo Transf, 7(6), 327-31, 1990.
Aleshire, SL, Osteen, KG, Maxson, WS, Entman, SS, Bradley, CA, Parl, FF. Localization of transferrin and its receptor in ovarian follicular cells: morphologic
studies in relation to follicular development. Fertil Steril, 51(3), 444-9, 1989.
Blackburn, DG, Osteen, KG, Winfrey, VP, Hoffman, LH. Obplacental giant cells of the domestic rabbit: development, morphology, and
intermediate filament composition. J Morphol, 202(2), 185-203, 1989.
Hill, GA, Freeman, M, Bastias, MC, Rogers, BJ, Herbert, CM, Osteen, KG, Wentz, AC. The influence of oocyte maturity and embryo quality on pregnancy rate in a
program for in vitro fertilization-embryo transfer. Fertil Steril, 52(5), 801-6, 1989.
Hill, GA, Osteen, KG. Follicular fluid steroid content and in vitro steroid secretion by granulosa-lutein
cells from individual follicles among different stimulation protocols for in vitro fertilization-embryo
transfer. J In Vitro Fert Embryo Transf, 6(4), 201-6, 1989.
Osteen, KG, Hill, GA, Hargrove, JT, Gorstein, F. Development of a method to isolate and culture highly purified populations
of stromal and epithelial cells from human endometrial biopsy specimens. Fertil Steril, 52(6), 965-72, 1989.
Segars, JH, Niblack, GD, Osteen, KG, Rogers, BJ, Wentz, AC. The human blastocyst produces a soluble factor(s) that interferes with lymphocyte
proliferation. Fertil Steril, 52(3), 381-7, 1989.
Skinner, MK, Osteen, KG. Developmental and hormonal regulation of bovine granulosa cell function in
the preovulatory follicle. Endocrinology, 123(3), 1668-75, 1988.
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